Prenyltransferase and squalene synthetase catalyze two important reactions in the sterol biosynthetic pathway. We will study the mechanisms of the Prenyl-transfer and head-to-head condensation reactions with substrate analogs whose reactivities differ from those of the natural substrates in a predictable manner. The head-to-head coupling reaction involves a complicated set of rearrangements as farnesyl pyrophosphate goes to presqualene pyrophosphate and on to squalene. Sulfur-containing substrate analogs will be prepared which can trap reactive intermediates during the rearrangement of presqualene pyrophosphate to squalene. The substrate analogs to be examined are potential, selective inhibitors of prenyl transferase and squalene synthetase and thus, offer a possibility for regulating sterol metabolism at the branch point to dolichols. To date no such selective inhibitor exists.